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INTRODUCTION: Transgender women are at increased risk of acquiring HIV. Earlier studies reported lower retention in HIV care, antiretroviral therapy uptake, adherence and viral suppression. We assessed the stages of the HIV care continuum of transgender women in the Netherlands over an 11-year period. In addition, we assessed new HIV diagnoses and late presentation, as well as disengagement from care, between 2011 and 2021. METHODS: Using data from the Dutch national ATHENA cohort, we separately assessed viral suppression, as well as time to achieving viral suppression, among transgender women for each year between 2011 and 2021. We also assessed trends in new HIV diagnoses and late presentation (CD4 count of <350 cells/µl and/or AIDS at diagnosis), and disengagement from care. RESULTS: Between 2011 and 2021, a total of 260 transgender women attended at least one HIV clinical visit. Across all years, <90% of transgender women were virally suppressed (207/239 [87%] in 2021). The number of new HIV diagnoses fluctuated for transgender women (ptrend = 0.053) and late presentation was common (ranging between 10% and 67% of new HIV diagnoses). Of the 260 transgender women, 26 (10%) disengaged from care between 2011 and 2021 (incidence rate = 1.10 per 100 person-years, 95% confidence interval = 0.75-1.61). CONCLUSIONS: Between 2011 and 2021, less than 90% of transgender women linked to HIV care were virally suppressed. Late presentation at the time of diagnosis and disengagement from care were common. Efforts are needed to identify barriers to early HIV diagnosis and to optimize the different steps across the care continuum for transgender women.
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Continuidad de la Atención al Paciente , Infecciones por VIH , Personas Transgénero , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/diagnóstico , Femenino , Personas Transgénero/estadística & datos numéricos , Países Bajos/epidemiología , Adulto , Continuidad de la Atención al Paciente/estadística & datos numéricos , Persona de Mediana Edad , Estudios de Seguimiento , Masculino , Fármacos Anti-VIH/uso terapéutico , Adulto Joven , Estudios de Cohortes , Recuento de Linfocito CD4 , Carga ViralRESUMEN
BACKGROUND: Men and women with a migration background comprise an increasing proportion of incident human immunodeficiency virus (HIV) cases across Western Europe. METHODS: To characterize sources of transmission in local transmission chains, we used partial HIV consensus sequences with linked demographic and clinical data from the opt-out AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort of people with HIV in the Netherlands and identified phylogenetically and epidemiologically possible HIV transmission pairs in Amsterdam. We interpreted these in the context of estimated infection dates, and quantified population-level sources of transmission to foreign-born and Dutch-born Amsterdam men who have sex with men (MSM) within Amsterdam transmission chains. RESULTS: We estimate that Dutch-born MSM were the predominant sources of infections among all Amsterdam MSM who acquired their infection locally in 2010-2021, and among almost all foreign-born Amsterdam MSM subpopulations. Stratifying by 2-year intervals indicated time trends in transmission dynamics, with a majority of infections originating from foreign-born MSM since 2016, although uncertainty ranges remained wide. CONCLUSIONS: Native-born MSM have predominantly driven HIV transmissions in Amsterdam in 2010-2021. However, in the context of rapidly declining incidence in Amsterdam, the contribution from foreign-born MSM living in Amsterdam is increasing, with some evidence that most local transmissions have been from foreign-born Amsterdam MSM since 2016.
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Background: Predicting cause-specific mortality among people with HIV (PWH) could facilitate targeted care to improve survival. We assessed discrimination of the Veterans Aging Cohort Study (VACS) Index 2.0 in predicting cause-specific mortality among PWH on antiretroviral therapy (ART). Methods: Using Antiretroviral Therapy Cohort Collaboration data for PWH who initiated ART between 2000 and 2018, VACS Index 2.0 scores (higher scores indicate worse prognosis) were calculated around a randomly selected visit date at least 1 year after ART initiation. Missingness in VACS Index 2.0 variables was addressed through multiple imputation. Cox models estimated associations between VACS Index 2.0 and causes of death, with discrimination evaluated using Harrell's C-statistic. Absolute mortality risk was modelled using flexible parametric survival models. Results: Of 59 741 PWH (mean age: 43 years; 80% male), the mean VACS Index 2.0 at baseline was 41 (range: 0-129). For 2425 deaths over 168 162 person-years follow-up (median: 2.6 years/person), AIDS (n = 455) and non-AIDS-defining cancers (n = 452) were the most common causes. Predicted 5-year mortality for PWH with a mean VACS Index 2.0 score of 38 at baseline was 1% and approximately doubled for every 10-unit increase. The 5-year all-cause mortality C-statistic was .83. Discrimination with the VACS Index 2.0 was highest for deaths resulting from AIDS (0.91), liver-related (0.91), respiratory-related (0.89), non-AIDS infections (0.87), and non-AIDS-defining cancers (0.83), and lowest for suicides/accidental deaths (0.65). Conclusions: For deaths among PWH, discrimination with the VACS Index 2.0 was highest for deaths with measurable physiological causes and was lowest for suicide/accidental deaths.
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INTRODUCTION: Mortality rates for people living with HIV (PLHIV) on antiretroviral therapy (ART) in high-income countries continue to decline. We compared mortality rates among PLHIV on ART in Europe for 2016-2020 with Spectrum's estimates. METHODS: The AIDS Impact Module in Spectrum is a compartmental HIV epidemic model coupled with a demographic population projection model. We used national Spectrum projections developed for the 2022 HIV estimates round to calculate mortality rates among PLHIV on ART, adjusting to the age/country distribution of PLHIV starting ART from 1996 to 2020 in the Antiretroviral Therapy Cohort Collaboration (ART-CC)'s European cohorts. RESULTS: In the ART-CC, 11,504 of 162,835 PLHIV died. Between 1996-1999 and 2016-2020, AIDS-related mortality in the ART-CC decreased from 8.8 (95% CI: 7.6 to 10.1) to 1.0 (0.9-1.2) and from 5.9 (4.4-8.1) to 1.1 (0.9-1.4) deaths per 1000 person-years among men and women, respectively. Non-AIDS-related mortality decreased from 9.1 (7.9-10.5) to 6.1 (5.8-6.5) and from 7.0 (5.2-9.3) to 4.8 (4.3-5.2) deaths per 1000 person-years among men and women, respectively. Adjusted all-cause mortality rates in Spectrum among men were near ART-CC estimates for 2016-2020 (Spectrum: 7.02-7.47 deaths per 1000 person-years) but approximately 20% lower in women (Spectrum: 4.66-4.70). Adjusted excess mortality rates in Spectrum were 2.5-fold higher in women and 3.1-3.4-fold higher in men in comparison to the ART-CC's AIDS-specific mortality rates. DISCUSSION: Spectrum's all-cause mortality estimates among PLHIV are consistent with age/country-controlled mortality observed in ART-CC, with some underestimation of mortality among women. Comparing results suggest that 60%-70% of excess deaths among PLHIV on ART in Spectrum are from non-AIDS causes.
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Síndrome de Inmunodeficiencia Adquirida , Epidemias , Infecciones por VIH , Adulto , Masculino , Humanos , Femenino , Países Desarrollados , Infecciones por VIH/tratamiento farmacológico , Distribución por EdadRESUMEN
BACKGROUND: Access to HIV testing is crucial for detection, linkage to treatment, and prevention. In less urbanised areas, reliance on general practitioners (GPs) for HIV testing is probable, as sexual health centres (SHC) are mostly located within urbanised areas. Limited insight into individuals undergoing HIV testing stems from sparse standard registration of demographics at GPs. This cross-sectional study aims (1) to assess and compare HIV testing at the GP and SHC, and (2) to assess population- and provider-specific HIV incidence. METHODS: Individual HIV testing data of GPs and SHC were linked to population register data (aged ≥ 15 years, Rotterdam area, 2015-2019). We reported the proportion HIV tested, and compared GP and SHC testing rates with negative binomial generalised additive models. Data on new HIV diagnoses (2015-2019) from the Dutch HIV Monitoring Foundation relative to the population were used to assess HIV incidence. RESULTS: The overall proportion HIV tested was 1.14% for all residents, ranging from 0.41% for ≥ 40-year-olds to 4.70% for Antilleans. The GP testing rate was generally higher than the SHC testing rate with an overall rate ratio (RR) of 1.61 (95% CI: 1.56-1.65), but not for 15-24-year-olds (RR: 0.81, 95% CI: 0.74-0.88). Large differences in HIV testing rate (1.36 to 39.47 per 1,000 residents) and GP-SHC ratio (RR: 0.23 to 7.24) by geographical area were observed. The GPs' contribution in HIV testing was greater for GP in areas further away from the SHC. In general, population groups that are relatively often tested are also the groups with most diagnoses and highest incidence (e.g., men who have sex with men, non-western). The overall incidence was 10.55 per 100,000 residents, varying from 3.09 for heterosexual men/women to 24.04 for 25-29-year-olds. CONCLUSIONS: GPs have a pivotal role in HIV testing in less urbanised areas further away from the SHC, and among some population groups. A relatively high incidence often follows relatively high testing rates. Opportunities to improve HIV testing have been found for migrants, lower-educated individuals, in areas less urbanised areas and further away from GP/SHC. Strategies include additional targeted testing, via for example SHC branch locations and outreach activities.
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Médicos Generales , Infecciones por VIH , Salud Sexual , Minorías Sexuales y de Género , Masculino , Humanos , Femenino , Países Bajos/epidemiología , Estudios Transversales , Incidencia , Homosexualidad Masculina , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & controlRESUMEN
BACKGROUND: A recent observational study suggested that the risk of cardiovascular events could be higher among antiretroviral therapy (ART)-naive individuals with HIV who receive integrase strand-transfer inhibitor (INSTI)-based ART than among those who receive other ART regimens. We aimed to emulate target trials separately in ART-naive and ART-experienced individuals with HIV to examine the effect of using INSTI-based regimens versus other ART regimens on the 4-year risk of cardiovascular events. METHODS: We used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. For the target trial in individuals who had previously never used ART (ie, ART-naive), eligibility criteria were aged 18 years or older, a detectable HIV-RNA measurement while ART-naive (>50 copies per mL), and no history of a cardiovascular event or cancer. Eligibility criteria for the target trial in those with previous use of non-INSTI-based ART (ie, ART-experienced) were the same except that individuals had to have been on at least one non-INSTI-based ART regimen and be virally suppressed (≤50 copies per mL). We assessed eligibility for both trials for each person-month between January, 2013, and January, 2023, and assigned individuals to the treatment strategy that was compatible with their data. We estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates. In per-protocol analyses, we censored individuals if they deviated from their assigned treatment strategy for more than 2 months and weighted uncensored individuals by the inverse of their time-varying probability of remaining uncensored. The denominator of the weight was estimated via a pooled logistic model that included baseline and time-varying covariates. FINDINGS: The analysis in ART-naive individuals included 10â767 INSTI initiators and 8292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15-45) and 52 in non-initiators (39 months; 18-47): standardised 4-year risks were 0·76% (95% CI 0·51 to 1·04) in INSTI initiators and 0·75% (0·54 to 0·98) in non-INSTI initiators; risk ratio 1·01 (0·57 to 1·57); risk difference 0·0089% (-0·43 to 0·36). The analysis in ART-experienced individuals included 7875 INSTI initiators and 373â965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9-29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15-37) in non-initiators: standardised 4-year risks 1·41% (95% CI 0·88 to 2·03) in INSTI initiators and 1·48% (1·28 to 1·71) in non-initiators; risk ratio 0·95 (0·60 to 1·36); risk difference -0·068% (-0·60 to 0·52). INTERPRETATION: We estimated that INSTI use did not result in a clinically meaningful increase of cardiovascular events in ART-naive and ART-experienced individuals with HIV. FUNDING: National Institute of Allergy and Infectious Diseases and National Institute on Alcohol Abuse and Alcoholism.
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Enfermedades Cardiovasculares , Infecciones por VIH , Inhibidores de Integrasa VIH , Adulto , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/efectos adversos , América del Norte , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Integrasas/uso terapéuticoRESUMEN
BACKGROUND: The widespread use of the integrase strand transfer inhibitor (INSTI) dolutegravir in first-line and second-line antiretroviral therapy (ART) might facilitate emerging resistance. The DTG RESIST study combined data from HIV cohorts to examine patterns of drug resistance mutations (DRMs) and identify risk factors for dolutegravir resistance. METHODS: We included cohorts with INSTI resistance data from two collaborations (ART Cohort Collaboration, International epidemiology Databases to Evaluate AIDS in Southern Africa), and the UK Collaborative HIV Cohort. Eight cohorts from Canada, France, Germany, Italy, the Netherlands, Switzerland, South Africa, and the UK contributed data on individuals who were viraemic on dolutegravir-based ART and underwent genotypic resistance testing. Individuals with unknown dolutegravir initiation date were excluded. Resistance levels were categorised using the Stanford algorithm. We identified risk factors for resistance using mixed-effects ordinal logistic regression models. FINDINGS: We included 599 people with genotypic resistance testing on dolutegravir-based ART between May 22, 2013, and Dec 20, 2021. Most had HIV-1 subtype B (n=351, 59%), a third had been exposed to first-generation INSTIs (n=193, 32%), 70 (12%) were on dolutegravir dual therapy, and 18 (3%) were on dolutegravir monotherapy. INSTI DRMs were detected in 86 (14%) individuals; 20 (3%) had more than one mutation. Most (n=563, 94%) were susceptible to dolutegravir, seven (1%) had potential low, six (1%) low, 17 (3%) intermediate, and six (1%) high-level dolutegravir resistance. The risk of dolutegravir resistance was higher on dolutegravir monotherapy (adjusted odds ratio [aOR] 34·1, 95% CI 9·93-117) and dolutegravir plus lamivudine dual therapy (aOR 9·21, 2·20-38·6) compared with combination ART, and in the presence of potential low or low (aOR 5·23, 1·32-20·7) or intermediate or high-level (aOR 13·4, 4·55-39·7) nucleoside reverse transcriptase inhibitor (NRTI) resistance. INTERPRETATION: Among people with viraemia on dolutegravir-based ART, INSTI DRMs and dolutegravir resistance were rare. NRTI resistance substantially increased the risk of dolutegravir resistance, which is of concern, notably in resource-limited settings. Monitoring is important to prevent resistance at the individual and population level and ensure the long-term sustainability of ART. FUNDING: US National Institutes of Health, Swiss National Science Foundation.
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Infecciones por VIH , Inhibidores de Integrasa VIH , Seropositividad para VIH , VIH-1 , Humanos , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Inhibidores de Integrasa VIH/uso terapéutico , Inhibidores de Integrasa VIH/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/farmacología , Lamivudine/uso terapéutico , Estudios de Cohortes , Seropositividad para VIH/tratamiento farmacológico , Farmacorresistencia Viral/genéticaRESUMEN
Background: The widespread use of the integrase strand transfer inhibitor (INSTI) dolutegravir (DTG) in first- and second-line antiretroviral therapy (ART) may facilitate emerging resistance. We combined data from HIV cohorts to examine patterns of drug resistance mutations (DRMs) and identify risk factors for DTG resistance. Methods: Eight cohorts from Canada, Europe, and South Africa contributed data on individuals with genotypic resistance testing on DTG-based ART. Resistance levels were categorised using the Stanford algorithm. We identified risk factors for resistance using mixed-effects ordinal logistic regression models. Results: We included 750 people with genotypic resistance testing on DTG-based ART between 2013 and 2022. Most had HIV subtype B (N=444, 59·2%) and were treatment-experienced; 134 (17.9%) were on DTG dual and 19 (2.5%) on DTG monotherapy. INSTI DRMs were detected in 100 (13·3%) individuals; 21 (2·8%) had more than one mutation. Most (N=713, 95·1%) were susceptible to DTG, 8 (1·1%) had potential-low, 5 (0·7%) low, 18 (2·4%) intermediate and 6 (0·8%) high-level DTG resistance. The risk of DTG resistance was higher on DTG monotherapy (adjusted odds ratio (aOR) 37·25, 95% CI 11·17 to 124·2) and DTG lamivudine dual therapy (aOR 6·59, 95% CI 1·70 to 25·55) compared to combination ART, and higher in the presence of potential-low/low (aOR 4.62, 95% CI 1.24 to 17.2) or intermediate/high-level (aOR 7·01, 95% CI 2·52 to 19·48) nucleoside reverse transcriptase inhibitors (NRTI) resistance. Viral load on DTG showed a trend towards increased DTG resistance (aOR 1·42, 95% CI 0·92 to 2·19 per standard deviation of log10 area under the viral load curve). Interpretation: Among people experiencing virological failure on DTG-based ART, INSTI DRMs were uncommon, and DTG resistance was rare. DTG monotherapy and NRTI resistance substantially increased the risk for DTG resistance, which is of concern, notably in resource-limited settings.
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INTRODUCTION: In Europe, half of people living with HIV (PLWH) present late to care, with associated higher morbidity and mortality. This study aims to assess short- and long-term costs of HIV-care based on time of presentation and identify other factors contributing to higher costs in the first and fifth year after antiretroviral therapy (ART) initiation. MATERIAL AND METHODS: We included ATHENA cohort data which prospectively includes 98% of PLWH in the Netherlands. PLWH who initiated ART in 2013 were included and followed over five years. PLWH were divided in three categories based on CD4 cell-count at time of ART initiation: timely presentation (CD4>350cells/µL), late presentation (CD4 200-350cells/µL or >350cells/µL with AIDS-defining illness) and very late presentation (CD4<200cells/µL). The total HIV-care cost was calculated distinguishing ART medication and non-ART medication costs (hospitalization, outpatient clinic visits, co-medications, and HIV-laboratory tests). RESULTS: From 1,296 PLWH, 273 (21%) presented late and 179 (14%) very late. Nearly half of those who entered HIV-care in a very late stage were of non-Dutch origin, with 21% originating from sub-Saharan Africa. The mean cost per patient in the first year was 12,902 (SD11,098), of which about two-thirds due to ART (8,250 (SD3,142)). ART costs in the first and fifth year were comparable regardless of time of presentation. During the first year on treatment, non-ART medication costs were substantially higher among those with late presentation (4,749 (SD8,009)) and very late presentation (15,886 (SD 21,834)), compared with timely presentation (2,407(SD4,511)). Higher non-ART costs were attributable to hospitalization and co-medication. The total non-ART costs incurred across five years on treatment were 56% and 246% higher for late and very late presentation respectively as compared to timely presentation. CONCLUSION: Very late presentation is associated with substantial costs, with non-ART costs nearly seven times higher than for those presenting timely. Hospitalization and co-medication costs are likely to continue to drive higher costs for individuals with late presentation into the future. Programs that identify individuals earlier will therefore likely provide significant short- and long-term health cost savings.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Adulto , Países Bajos/epidemiología , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Costos de la Atención en Salud , Hospitalización , Europa (Continente) , Recuento de Linfocito CD4 , Fármacos Anti-VIH/uso terapéuticoRESUMEN
OBJECTIVE: Timely identification of acute or early HIV infection (AEHI) is important to help prevent onward transmission, and understanding the number of secondary infections resulting from individuals with AEHI is key to planning HIV prevention services and case finding. DESIGN: We performed a phylogenetic investigation of a dense sample of individuals with AEHI who took part in the Netherlands Cohort Study on Acute HIV infection (NOVA) in the Netherlands during 2015-2021. METHODS: Transmission clusters were identified using phylogenetic analyses based on HIV pol sequences. The Tamura-Nei model was used to estimate genetic distance. A number of 1000 bootstraps was used to check the reliability of clustering using maximum likelihood. A cluster was defined as having a bootstrap value of at least 95% and a genetic distance of at most 1.5%. Sensitivity analyses using different values for the bootstrap and genetic distance were performed to study the reproducibility of the clustering. RESULTS: Of the 156 participants included in NOVA between July 2015 and April 2021, 134 individuals for whom baseline characteristics and genotypic resistance data at baseline were available could be included. We identified 10 clusters, but the majority of persons (111/134) were not part of a cluster, suggesting mainly independent transmission events. CONCLUSION: Mainly independent transmission events among a study population consisting predominantly of MSM in a low-incidence high-resource setting is likely the result of active AEHI case finding and direct start of treatment, and the roll-out over recent years of preventive measures such as preexposure prophylaxis.
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Infecciones por VIH , Humanos , Masculino , Infecciones por VIH/epidemiología , Reproducibilidad de los Resultados , Estudios de Cohortes , Filogenia , Brotes de Enfermedades/prevención & control , Homosexualidad Masculina , Análisis por ConglomeradosRESUMEN
INTRODUCTION: Randomized trials and observational studies have consistently reported rates of sustained virological response (SVR), equivalent to hepatitis C virus (HCV) cure, as high as 95% following treatment with direct-acting antiviral (DAA) treatment in individuals with HIV and HCV co-infection. However, large studies assessing whether SVR rates differ according to demographic and clinical strata are lacking. Additionally, the SVR rates reported in the literature were typically computed in non-random samples of individuals with available post-DAA HCV-RNA measures. Here, we aimed to estimate the probability of SVR after DAA treatment initiation in persons with HIV and HCV co-infection overall and by demographic and clinical characteristics with and without adjustment for missing HCV-RNA testing. METHODS: We included adults with HIV-HCV co-infection who received DAA treatment between 2014 and 2020 in HepCAUSAL, an international collaboration of cohorts from Europe and North America. We estimated the proportions of DAA recipients who had documented SVR (defined as an undetectable HCV-RNA at least 12 weeks after the end of DAA treatment) overall and by strata defined by age, sex, presence of cirrhosis, calendar period, mode of HIV acquisition, CD4 cell count and HCV genotype at DAA treatment. We then compared these rates with those obtained using the parametric g-formula to impute SVR status for individuals with no SVR assessment. RESULTS AND DISCUSSION: A total of 4527 individuals who initiated DAA treatment (88% males, median [IQR] age 56 [50, 62] years) were included. Of the total of 642 (14%) individuals had no HCV-RNA test on or after 12 weeks after the end of treatment. The overall observed and g-formula imputed SVR rates were 93% (95% CI 93, 94) and 94% (95% CI 92, 95), respectively. SVR estimates were similarly high across all strata. A substantial proportion of individuals who received DAA treatment were never assessed for SVR post-DAA and strategies for more systematic routine HCV-RNA testing should be considered. CONCLUSIONS: Our estimates with and without adjustment for missing HCV-RNA testing indicate SVR rates of approximately 95%, like those reported in clinical trials.
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Coinfección , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Adulto , Masculino , Humanos , Persona de Mediana Edad , Femenino , Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis C/tratamiento farmacológico , Hepacivirus/genética , ARN/uso terapéutico , Resultado del TratamientoRESUMEN
Background: More than 300 cities including the city of Amsterdam in the Netherlands have joined the UNAIDS Fast-Track Cities initiative, committing to accelerate their HIV response and end the AIDS epidemic in cities by 2030. To support this commitment, we aimed to estimate the number and proportion of Amsterdam HIV infections that originated within the city, from Amsterdam residents. We also aimed to estimate the proportion of recent HIV infections during the 5-year period 2014-2018 in Amsterdam that remained undiagnosed. Methods: We located diagnosed HIV infections in Amsterdam using postcode data (PC4) at time of registration in the ATHENA observational HIV cohort, and used HIV sequence data to reconstruct phylogeographically distinct, partially observed Amsterdam transmission chains. Individual-level infection times were estimated from biomarker data, and used to date the phylogenetically observed transmission chains as well as to estimate undiagnosed proportions among recent infections. A Bayesian Negative Binomial branching process model was used to estimate the number, size, and growth of the unobserved Amsterdam transmission chains from the partially observed phylogenetic data. Results: Between 1 January 2014 and 1 May 2019, there were 846 HIV diagnoses in Amsterdam residents, of whom 516 (61%) were estimated to have been infected in 2014-2018. The rate of new Amsterdam diagnoses since 2014 (104 per 100,000) remained higher than the national rates excluding Amsterdam (24 per 100,000), and in this sense Amsterdam remained a HIV hotspot in the Netherlands. An estimated 14% [12-16%] of infections in Amsterdan MSM in 2014-2018 remained undiagnosed by 1 May 2019, and 41% [35-48%] in Amsterdam heterosexuals, with variation by region of birth. An estimated 67% [60-74%] of Amsterdam MSM infections in 2014-2018 had an Amsterdam resident as source, and 56% [41-70%] in Amsterdam heterosexuals, with heterogeneity by region of birth. Of the locally acquired infections, an estimated 43% [37-49%] were in foreign-born MSM, 41% [35-47%] in Dutch-born MSM, 10% [6-18%] in foreign-born heterosexuals, and 5% [2-9%] in Dutch-born heterosexuals. We estimate the majority of Amsterdam MSM infections in 2014-2018 originated in transmission chains that pre-existed by 2014. Conclusions: This combined phylogenetic, epidemiologic, and modelling analysis in the UNAIDS Fast-Track City Amsterdam indicates that there remains considerable potential to prevent HIV infections among Amsterdam residents through city-level interventions. The burden of locally acquired infection remains concentrated in MSM, and both Dutch-born and foreign-born MSM would likely benefit most from intensified city-level interventions. Funding: This study received funding as part of the H-TEAM initiative from Aidsfonds (project number P29701). The H-TEAM initiative is being supported by Aidsfonds (grant number: 2013169, P29701, P60803), Stichting Amsterdam Dinner Foundation, Bristol-Myers Squibb International Corp. (study number: AI424-541), Gilead Sciences Europe Ltd (grant number: PA-HIV-PREP-16-0024), Gilead Sciences (protocol numbers: CO-NL-276-4222, CO-US-276-1712, CO-NL-985-6195), and M.A.C AIDS Fund.
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Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Teorema de Bayes , Ciudades/epidemiología , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Humanos , Masculino , FilogeniaRESUMEN
Set-point viral load (SPVL), a common measure of human immunodeficiency virus (HIV)-1 virulence, is partially determined by viral genotype. Epidemiological evidence suggests that this viral property has been under stabilising selection, with a typical optimum for the virus between 104 and 105 copies of viral RNA per ml. Here we aimed to detect transmission fitness differences between viruses from individuals with different SPVLs directly from phylogenetic trees inferred from whole-genome sequences. We used the local branching index (LBI) as a proxy for transmission fitness. We found that LBI is more sensitive to differences in infectiousness than to differences in the duration of the infectious state. By analysing subtype-B samples from the Bridging the Evolution and Epidemiology of HIV in Europe project, we inferred a significant positive relationship between SPVL and LBI up to approximately 105 copies/ml, with some evidence for a peak around this value of SPVL. This is evidence of selection against low values of SPVL in HIV-1 subtype-B strains, likely related to lower infectiousness, and perhaps a peak in the transmission fitness in the expected range of SPVL. The less prominent signatures of selection against higher SPVL could be explained by an inherent limit of the method or the deployment of antiretroviral therapy.
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OBJECTIVES: To assess differences in socio-demographics, HIV testing and healthcare seeking behavior between individuals diagnosed late and those diagnosed early after HIV-acquisition. DESIGN: Cross-sectional study among recently HIV-diagnosed migrant and non-migrant individuals living in the Netherlands. METHODS: Participants self-completed a questionnaire on socio-demographics, HIV-testing and healthcare seeking behavior preceding HIV diagnosis between 2013-2015. Using multivariable logistic regression, socio-demographic determinants of late diagnosis were explored. Variables on HIV-infection, testing and access to care preceding HIV diagnosis were compared between those diagnosed early and those diagnosed late using descriptive statistics. RESULTS: We included 143 individuals with early and 101 with late diagnosis, of whom respectively 59/143 (41%) and 54/101 (53%) were migrants. Late diagnosis was significantly associated with older age and being heterosexual. Before HIV diagnosis, 89% of those with early and 62% of those with late diagnosis had ever been tested for HIV-infection (p<0.001), and respectively 99% and 97% reported healthcare usage in the Netherlands in the two years preceding HIV diagnosis (p = 0.79). Individuals diagnosed late most frequently visited a general practitioner (72%) or dentist (62%), and 20% had been hospitalized preceding diagnosis. In these settings, only in respectively 20%, 2%, and 6% HIV-testing was discussed. CONCLUSION: A large proportion of people diagnosed late had previously tested for HIV and had high levels of healthcare usage. For earlier-case finding of HIV it therefore seems feasible to successfully roll out interventions within the existing healthcare system. Simultaneously, efforts should be made to encourage future repeated or routine HIV testing among individuals whenever they undergo an HIV test.
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Infecciones por VIH , Migrantes , Estudios Transversales , Diagnóstico Tardío , Atención a la Salud , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Humanos , Países Bajos/epidemiologíaRESUMEN
We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.
Asunto(s)
Infecciones por VIH/virología , VIH-1/patogenicidad , Adulto , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Evolución Molecular , Femenino , Genoma Viral , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/transmisión , VIH-1/genética , VIH-1/fisiología , Humanos , Masculino , Mutación , Países Bajos , Filogenia , Carga Viral , VirulenciaRESUMEN
OBJECTIVE: The aim of this study was to investigate introductions and spread of different HIV-1 subtypes in the Netherlands. DESIGN: We identified distinct HIV-1 transmission chains in the Netherlands within the global epidemic context through viral phylogenetic analysis of partial HIV-1 polymerase sequences from individuals enrolled in the ATHENA national HIV cohort of all persons in care since 1996, and publicly available international background sequences. METHODS: Viral lineages circulating in the Netherlands were identified through maximum parsimony phylogeographic analysis. The proportion of HIV-1 infections acquired in-country among heterosexuals and MSM was estimated from phylogenetically observed, national transmission chains using a branching process model that accounts for incomplete sampling. RESULTS: As of 1 January 2019, 2589 (24%) of 10â971 (41%) HIV-1 sequenced individuals in ATHENA had non-B subtypes (A1, C, D, F, G) or circulating recombinant forms (CRF01AE, CRF02AG, CRF06-cpx). The 1588 heterosexuals were in 1224, and 536 MSM in 270 phylogenetically observed transmission chains. After adjustments for incomplete sampling, most heterosexual (75%) and MSM (76%) transmission chains were estimated to include only the individual introducing the virus (sizeâ=â1). Onward transmission occurred mostly in chains size 2-5 amongst heterosexuals (62%) and in chains size at least 10 amongst MSM (64%). Considering some chains originated in-country from other risk-groups, 40% (95% confidence interval: 36-44) of non-B-infected heterosexuals and 62% (95% confidence interval: 49-73) of MSM-acquired infection in-country. CONCLUSION: Although most HIV-1 non-B introductions showed no or very little onward transmission, a considerable proportion of non-B infections amongst both heterosexuals and MSM in the Netherlands have been acquired in-country.
Asunto(s)
Infecciones por VIH , VIH-1 , VIH-1/genética , Heterosexualidad , Homosexualidad Masculina , Humanos , Masculino , Países Bajos/epidemiología , FilogeniaRESUMEN
BACKGROUND: HIV is now considered a chronic condition, and people living with HIV, when treated, have a similar life expectancy as compared to the general population. Consequently, improving and ensuring a good health-related quality of life (HrQoL) among people living with HIV (people living with HIV) is increasingly important and has risen on the global agenda in recent years. A 'fourth 90' as 90% of people with viral load suppression have a good HrQoL should therefore be adopted alongside the other 90-90-90 targets. This study aims to report the progress on HrQoL as the 'fourth 90' and compare against the general population in the Netherlands and England. METHODS: In the Netherlands, individuals attending the HIV outpatient clinic of a tertiary hospital were asked to complete the EQ-5D-5L from June 2016 until December 2018. In England, individuals attending one of 73 HIV outpatient clinics were randomly sampled to complete the Positive Voices survey, which included the EQ-5D-5L, from January to September 2017. HrQoL scores were combined with demographic data and compared to general population data. FINDINGS: The EQ-5D-5L was filled-out by 895 people living with HIV in the NL and 4,137 in England. HrQoLutility was 0·85 among Dutch and 0·83 among English people living with HIV. This equated to 98% and 94% of the general population HrQoLutility in the Netherlands and England, respectively. Of the EQ-5D domains, anxiety/depression was mostly affected, with one-third in Dutch (35%) and almost half (47%) of English people living with HIV reporting symptoms. This was higher compared to their respective general populations (21% NL and 31% England). INTERPRETATION: Overall, HrQoLutility for people living with HIV was high in both countries and highly comparable to the general populations Nevertheless, there should be an increased focus on anxiety and depression in the people living with HIV population The EQ-5D-5L proved an easy HrQoL measurement tool and identified areas for improvement by social and behavioural interventions. FUNDING: The study received funding (unrestricted grants) from: Gilead sciences, ViiV Healthcare, MSD, and Jansen pharmaceuticals.
RESUMEN
OBJECTIVES: To assess the cost-effectiveness of a preexposure prophylaxis (PrEP) programme offering a choice of daily and event-driven PrEP for men who have sex with men (MSM) in the Netherlands. METHODS: We used an agent-based transmission model and an economic model to simulate a programme offering only daily PrEP and a programme offering daily and event-driven PrEP. Use of PrEP medication and preference for daily versus event-driven PrEP were estimated from the Amsterdam PrEP Demonstration Project (AMPrEP). We calculated costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios (ICER), over 2018-2027. An ICER less than 20 000 per QALY gained was considered cost-effective. RESULTS: Using AMPrEP data, we estimated that 27% of PrEP users chose event-driven PrEP with a median of 12 pills per month; daily PrEP users used a median of 30 pills per month. With PrEP, 3740 HIV infections were averted and 1482 QALYs were gained over 2018-2027, compared to the scenario without PrEP. The probability of the PrEP programme being cost-effective (compared to not having a PrEP programme) increased from 91% with daily PrEP to 94% with a choice of daily and event-driven PrEP. The probability of being cost-saving increased from 42% with only daily PrEP to 48% with choice of daily and event-driven PrEP. CONCLUSIONS: A daily PrEP programme for MSM would be cost-effective. Providing a choice of daily and event-driven PrEP can result in savings and is more likely to be cost-effective and cost-saving, compared to a programme offering only daily PrEP.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Fármacos Anti-VIH/uso terapéutico , Análisis Costo-Beneficio , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Humanos , Masculino , Países BajosRESUMEN
BACKGROUND: Migrant populations are overrepresented among persons diagnosed with HIV in the European Union and the European Economic Area. Understanding the timing of HIV acquisition (premigration or postmigration) is crucial for developing public health interventions and for producing reliable estimates of HIV incidence and the number of people living with undiagnosed HIV infection. We summarize a recently proposed method for determining the timing of HIV acquisition and apply it to both real and simulated data. METHODS: The considered method combines estimates from a mixed model, applied to data from a large seroconverters' cohort, with biomarker measurements and individual characteristics to derive probabilities of premigration HIV acquisition within a Bayesian framework. The method is applied to a subset of data from the European Surveillance System (TESSy) and simulated data. FINDINGS: Simulation study results showed good performance with the probabilities of correctly classifying a premigration case or a postmigration case being 87.4% and 80.4%, respectively. Applying the method to TESSy data, we estimated the proportions of migrants who acquired HIV in the destination country were 31.9%, 37.1%, 45.3%, and 45.2% for those originating from Africa, Europe, Asia, and other regions, respectively. CONCLUSIONS: Although the considered method was initially developed for cases with multiple biomarkers' measurements, its performance, when applied to data where only one CD4 count per individual is available, remains satisfactory. Application of the method to TESSy data, estimated that a substantial proportion of HIV acquisition among migrants occurs in destination countries, having important implications for public health policy and programs.